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Risk factors for hearing loss from meningitis in children: the Children's Hospital experience.

OBJECTIVES: To identify statistically significant risk factors for hearing loss in children with meningitis, determine the overall incidence of hearing loss in a large group of children with confirmed meningitis, and quantify the percentage of children with progressive or fluctuating hearing loss after meningitis. DESIGN: Retrospective analysis. PATIENTS AND OTHER PARTICIPANTS: Four hundred thirty-two children admitted to the Children's Hospital, Birmingham, Ala, from January 1, 1985, to December 31, 1995, with the diagnosis of meningitis. RESULTS: Of 432 children with meningitis, 59 (13.7%) had the development of hearing loss. Of these 59 children, 46 (78.0%) had stable sensorineural hearing loss and 13 (22.0%) had either progressive or fluctuating hearing loss. Of the variables examined using multiple logistic regression backward-elimination modeling, only 5 appeared to be significantly associated with the development of hearing loss: computed tomographic scan evidence of increased intracranial pressure (estimated odds ratio [OR] = 2.3), male sex (OR= 1.9), the common logarithm of glucose levels in the cerebrospinal fluid (OR = 0.58), Streptococcus pneumoniae as the causative organism (OR= 2.1), and the presence of nuchal rigidity (OR = 1.9). In the children with progressive hearing loss, the time for progression varied from 3 months to 4 years before hearing stabilized. CONCLUSIONS: In this study of children diagnosed as having meningitis, hearing loss developed in 59 (13.7%). Forty-six (78.0%) of these children with hearing loss had stable auditory thresholds over time, and 13 (22.0%) exhibited deterioration or fluctuation of acuity over time. Evidence of increased intracranial pressure by computed tomographic scan, male sex, low glucose levels in the patients' cerebrospinal fluid, S pneumoniae as the causative organism, and the presence of nuchal rigidity appear to be significant predictors for future hearing loss.

Child, Preschool↗

Risk factors for ototoxicity due to cisplatin.

OBJECTIVE: To determine whether abnormalities in routine blood tests were associated with increased susceptibility to hearing loss induced by cisplatin chemotherapy. DESIGN: Cohort study of patients with head and neck cancer receiving cisplatin chemotherapy who underwent audiometric testing. SETTING: A large, university-based hospital; part of a larger study regarding rehabilitation of patients with cancer. PATIENTS: Forty-two patients with head and neck cancer who agreed to participate underwent at least three serial treatments with high-dose cisplatin therapy. Routine blood tests and audiometric testing were performed before each course of chemotherapy. One hundred eighty audiograms were performed. OUTCOME MEASURES: A deterioration of auditory threshold of 15 dB or more at one frequency or of 10 dB or more at three or more frequencies was considered a significant loss. Only frequencies at and below 4000 Hz were considered. RESULTS: Multiple analysis of variance results indicated that decreased serum albumin level, hemoglobin level, red blood cell count, and hematocrit were associated with an increased likelihood of significant hearing loss during chemotherapy. CONCLUSIONS: Patients in poor general medical condition with low levels of red blood cells or serum proteins are at increased risk for development of hearing loss from cisplatin chemotherapy. We recommend that hearing be tested before chemotherapy begins and after the first course of cisplatin. If there is no significant hearing loss at or below 4000 Hz at that time, then subsequent audiometric testing is required only if symptoms of hearing loss develop.

Adult↗

Improved treatment of sudden hearing loss by specific fibrinogen aphaeresis.

The etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14-16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1-15, 1986; Harris and Sharp, Laryngoscope 100:516-524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41-45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94-100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763-766, 1999; Suckfüll, Lancet 360:1811-1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641-645, 1996; Suckfüll et al., Otol. Neurotol. 23:309-311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1-3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80-100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 +/- 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 +/- 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen. In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss.

Adsorption↗

Behavioral effects and binding affinities of two stereoisomeric psychotomimetic glycolates.

A comparison was made of the behavioral effects in cats of the dextro and levo isomers of 3-quinuclidinyl benzilate (QB), using a special computer-controlled program. Such psychophysical parameters as rate of response and tendency to use the left or right paw for lever pressing were used primarily to evaluate drug efficacy. The drug did not alter auditory threshold or the percentage of errors in lever pressing. The l-isomer was found to be at least 100 times as potent as the d-isomer, the effects of both being qualitatively similar. After a single dose of 5 mug/Kg of 1-QB, the cats' performance did not return to normal until 5-7 days later. Pretreatment of the cats with a dose of 2 mg/Kg of atropine, an antimuscarinic agent, did not prevent the behavioral effects of 1-QB. The binding affinity of two isomers for synaptic membranes and phosphatidyl serine was identical.

Animals↗

Hypothyroidism and the ear: electrophysiological, morphological, and chemical considerations.

There is both clinical and laboratory evidence that hearing loss can result from congenital and acquired hypothyroidism. The reversibility of this process, however, and its incidence and pathophysiology are not universally agreed upon. Laboratory animals rendered hypothyroid with radioactive iodine 131 or propylthiouracil demonstrated normal perilymph sodium and potassium levels but increased auditory thresholds for N1N2 response and brain stem evoked audiometry as well as a crystallized consistency of the bone of the bullae and cochleae, ossicular abnormalities, obliteration of the oval and round window, large dark staining lipid accumulations in Hensen's cells, large intercellular spaces in the stria vascularis with degeneration of the marginal and intermediate cells, inner and outer hair cell degeneration, debris in the cochlear duct, and tectorial membrane irregularity. Otic capsule biochemical alterations were identified which may account for the osseous changes observed morphologically. The morphological, biochemical, and electrophysiological findings in this study support the hypothesis that the cochlea is a site of lesion for sensorineural hearing loss in hypothyroidism. Middle ear changes identified could be responsible for the conductive component.

Animals↗

Auditory sensitivity in the great tit: perception of signals in the presence and absence of noise.

Absolute and masked auditory thresholds (critical masking ratios) were determined behaviourally in the great tit, Parus major, using a GO/NOGO-procedure. Absolute sensitivity was measured between 0.25 and 10 kHz. In the absence of noise, great tits were most sensitive to frequencies between 2 and 4 kHz. In background noise, however, the sensitivity was only a function of the noise level and was independent of frequency. Critical masking ratios determined for signals between 0.25 and 8 kHz were almost constant (median values varied between 23.8 and 25.9 dB) irrespective of signal frequency. Therefore, in contrast to the majority of bird species, great tits have unusually low critical masking ratios at high frequencies. This means that great tits can use high-frequency vocalizations to communicate efficiently in noisy (i.e. natural) environments. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Noctuid moths show neural and behavioural responses to sounds made by some bat-marking rings.

Coloured rings are often used for marking bats so that specific individuals can be recognized. We noticed that the rings of mouse-eared bats, Myotis myotis and Myotis blythii, in a combination of one plastic-split and one metallic ring on the same forearm, emitted sounds that were largely ultrasonic each time the rings met in flight. We recorded the ring sounds and the echolocation calls produced by the bats, and played them back to neural preparations of lesser yellow underwing moths, Noctua comes, while making extracellular recordings from the moths' A1 auditory receptors. The peak energy of the ring sounds occurred much closer in frequency to the moth's best auditory frequency (the frequency at which the moth has the lowest auditory threshold) than the peak energy of the calls, for both bat species, and the ring sounds were detected at a threshold 5-6 dB peSPL lower than the calls. Moths performed evasive manoeuvres to playbacks of ring sounds more frequently than they did to control (tape noise) sequences. These neural and behavioural responses imply that certain bats should not be marked with two rings on one wing, as this may make the bat more apparent to tympanate insects, and may therefore reduce its foraging success. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Binaural influences on Doppler shift compensation of the horseshoe bat Rhinolophus rouxi.

The flying horseshoe bat Rhinolophus rouxi compensates for Doppler shifts in echoes of their orientation pulses. By lowering the frequency of subsequent calls the echo's constant frequency is stabilized at the so-called reference frequency centered in a narrow and sensitive cochlear filter. This audio-vocal behaviour is known as Doppler shift compensation. To investigate whether the bats depend on binaural cues when compensating, three animals were tested for compensation on a swing before and after unilateral deafening. In each case compensation was severely impaired by unilateral deafening. Individual animals' compensation amplitude was reduced to 28-48% of the preoperational compensation of a +1.8 kHz shift. Doppler shift compensation performance did not recover to control levels during the observed period of 24 h after surgery. In contrast, unilateral middle ear removal which induces a unilateral auditory threshold increase of 9-14 dB does not impair compensation performance on the swing. To mimick Doppler shifts in a fixed setup, the frequencies of recorded echolocation calls were experimentally shifted between 0 and +2 kHz and played back via earphones to six animals. The bats completely compensated the experimental shifts only as long as the interaural intensity difference of the playback did not exceed 20 dB. No animal compensated with monaural playback.

Adaptation, Physiological↗

Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients.

OBJECTIVE: Test of dose-response relationship for Ginkgo biloba extract EGb 761 (oral) in outpatients with acute idiopathic sudden sensorineural hearing loss (ISSHL) of at least 15 dB at one frequency within the speech range occurring less than 10 days before study inclusion. DESIGN: Multicentre, randomized, double-blind phase III study comparing dosages of 120 mg twice daily and 12 mg twice daily over 8 weeks. MAIN ENDPOINT: Recovery (in dB) of the auditory threshold from the initial measurement to the value on the last day of treatment, averaged over those frequencies from 0.25, 0.5, 1, 2, and 3 kHz for which the initial hearing loss amounted to 15 dB or more compared to the level on the opposite side. PATIENTS: 106 patients with an average age of 44+/-16 years and with hearing loss at affected frequencies 26 dB +/- 9 dB included between December 1995 and July 1997. RESULTS: Large majorities of both treatment groups recovered completely. In exploratory analyses of the 96 patients included according to the protocol, patients given the higher dose had less risk of not recovering well (< or =10 dB residual hearing loss) (one-sided Fisher test: P = 0.0061), especially if they had no tinnitus (n = 44, P = 0.00702). CONCLUSION: A higher dosage of EGb 761 (oral) appears to speed up and secure the recovery of ISSHL patients, with a good chance that they will recover completely, even with little treatment. This was already observed after one week of treatment. We find it justified to treat patients who have unilateral ISSHL of less than 75 dB and neither tinnitus nor vertigo with 120 mg oral EGb 761 twice daily.

Acute Disease↗

Morphological changes in the cochlea of the mouse after the onset of hearing.

The cochleae of 5, 10, 12 and 15 day old mice and of adults (Mus musculus, strain NMRI) were studied by light and electron microscopy. In each case the same part of the organ of Corti (2.8-3.3 mm from the helicotrema) was examined. The results were correlated with the development of auditory thresholds (in mice of the same strain) obtained by Ehret (Ehret, G. (1971) J. Am. Audiol. Soc. 1, 179-184). It was demonstrated that morphological development of the organ of Corti is by no means complete at the onset of behavioural responses to acoustic stimuli. After this event the following morphological changes occur: (1) The basilar membrane filaments stain more intensely and the tympanic cover layer is greatly reduced in thickness and almost completely disappears. (2) The filaments of the pillar cells stain more intensely and apparently increase in number, and the angle between the outer and inner pillar cells increases so that the cross-sectional area of the tunnel of Corti expands. (3) Hook-shaped connections (marginal pillars) between the reticular membrane and the tectorial membrane disappear. The consequences of these morphological changes for the cochlear mechanics are discussed, especially in respect to the increase of sensitivity of hearing.

Animals↗

Threshold integration of bi-amplitude signals.

This study examined the pattern of intensity integration at threshold. The stimuli studied are unique in that they have a compound peak-to-peak amplitude envelope. This waveform was partitioned into two segments, each having a different peak-to-peak magnitude (bi-amplitude). All signals in the bi-amplitude series were the same duration (100 ms). Therefore, threshold differences between these signals are due solely to the integration of intensity in the amplitude dimension. A prediction of the pattern of thresholds, based on the diverted-input hypothesis, suggested that little or no integration would occur when the amplitude difference between segments is greater than a specific magnitude. Our results indicate that there are similarities in the integration process found with variable duration signals and with bi-amplitude signals. We conclude that previous estimates of the minimum intensity level based on temporal integration data underestimates the intensity levels that can contribute to threshold. Our results suggest that there are no apparent constraints on the intensity levels that can be integrated near threshold. The auditory system integrates distributed stimulus intensity in both the time and amplitude dimensions. Temporal integration in the auditory system can be viewed as a signal process, where an enhanced internal representation is given low-level stimuli.

Acoustic Stimulation↗

Developmental neurotoxicity following neonatal exposure to 3,3'-iminodipropionitrile in the rat.

Adult exposure to the neurotoxicant 3,3'-iminodipropionitrile (IDPN), induces a hyperkinetic syndrome consisting of spontaneous head movements, abnormal circling, backward locomotion, and sensory disruption. We report here the behavioral effects of developmental exposure to IDPN in the rat. Animals were exposed (IP) to either saline, 75, 150, or 300 mg/kg/day on postnatal days (PND) 5-7. Animals were tested for: Figure-8 maze activity (PND 13-60); olfactory discrimination learning (PND 18 & 24); T-maze alternation and position discrimination learning (PND 25 & 26); acoustic startle response (PND 23, 61, & 62); passive avoidance (PND 70). To better define the dose response, a separate group of animals was exposed to either saline or 225 mg/kg/day (PND 5-7) and tested in the activity, T-maze, and startle paradigms. Animals exposed to 225 mg/kg/day and 300 mg/kg/day had decreased weight gain and lethality was 25% in the latter group. Signs of the IDPN syndrome, evident in the 225 and 300 mg/kg/day groups, persisted throughout the course of the study. IDPN exposed animals (300 mg/kg/day) were hyperactive on PND 17-60, failing to develop habituation in the Figure-eight maze until PND 60. The acoustic startle response was depressed for the 225 and 300 mg/kg/day groups on PND 23 only. Auditory thresholds were elevated for a high-frequency (40 kHz) but not a low-frequency tone (5 kHz) for the 225 and 300 mg/kg/day groups, indicating a hearing loss. IDPN treatment also disrupted performance of olfactory discrimination learning and produced cognitive deficits in T-maze learning in infants (300 mg/kg/day). That cognitive deficits also appeared in adulthood (PND 70) was demonstrated by learning deficits in a passive avoidance task at 150 and 300 mg/kg/day. IDPN (300 mg/kg/day) also caused a decrease in the wet weight of the whole brain (8%) and the cerebellum (12%) but not the hippocampus. These data demonstrate that short-term, neonatal exposure to IDPN in the rat produced persistent alterations in sensory, motor, and cognitive aspects of nervous system function.

Animals↗

Bromate-induced ototoxicity.

For decades, it has been known that ingested potassium bromate and sodium bromate can induce hearing loss. Hearing loss onset, following high-dose ingestion, is generally rapid occurring within 4-16 h and of a severe to profound degree. Unlike the sensorineural hearing loss which is generally irreversible, bromate-induced tinnitus, which is less well-studied, may reportedly be permanent or temporary. It is not clear whether actual bromate-induced vestibulotoxicity occurs in clinical populations. The primary sites of lesion for bromate-induced ototoxicity appear to be in the cochlea. However, possible effects on the VIIIth nerve and central auditory system have not been fully investigated. Based on animal studies, in the cochlea, bromate damages the stria vascularis, Reissner's membrane, inner and outer hair cells, Claudius cells and inner sulcus cells. Physiologically, bromate reduces the endocochlear potential, cochlear microphonics, and electrophysiologic auditory thresholds. Possible mechanisms are discussed. The effects of long-term low-dose bromate exposure on hearing have not been studied. These effects, if they occur, may not be readily detected in many clinical populations, because idiopathic hearing loss occurs commonly in the population as a whole. Further it is unknown whether or not chronic bromate ingestion may exacerbate noise-induced hearing loss. Further study to determine the maximum safe exposure level for long-term administration and to develop possible antidotes is warranted.

Animals↗

Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests.

Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBPdelta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning.

Animals↗

Audiometric and vestibular evaluation in women using the hormonal contraceptive method.

AIM: To co-relate the use of hormonal contraceptives with positive Auditory and Vestibular alterations. METHODS: medical history taking, audiometric test and vestibular test was applied to 60 women between the ages of 14 and 35 years old, and 30 of these women are on oral hormonal contraceptive consisting of Estrogen and Progesterone (risk group), for 6 months or more, that had no Auditory or Vestibular complaints prior to the usage of hormones; and 30 women that had never used these hormones (control group), with no Auditory or Vestibular complaints. Medical history was used to select the sample. RESULTS: Based on otoneurological findings, through quantitative research, we could see the prevailing Irritatative Peripheral Vestibular Syndrome and tinnitus in the risk group, without audiometric alterations. CONCLUSION: The use of oral contraceptives can provoke functional alterations in the inner ear, specially tinnitus and Irritative Peripheral Vestibular Syndrome in the risk group; but auditory threshold alterations were not evident.

Adolescent↗

Myringoplasty for the anterior perforation: experience with the Kerr flap.

Surgical closure of the anteriorly located tympanic membrane perforation can present a problem. The lack of anterior support for the graft frequently leads to graft failure if an underlay method is used whereas anterior blunting is a complication of onlay techniques in this situation. The experience with the Kerr flap, an underlay graft fashioned to include a tab of fascia which is placed laterally under the annulus and the anterior meatal skin, is presented. This method gave a 97.5 percent closure rate with no cases of anterior marginal blunting and a mean auditory threshold gain of 8.5 dB (95 percent confidence limits 5 to 11.9 dB, P less than 0.01) was achieved at the frequencies tested. The use of the Kerr flap is recommended when repairing the anteriorly placed tympanic membrane perforation.

Adolescent↗

Interhemispheric transfer in schizophrenics, depressives, and normals with schizoid tendencies.

Although several studies suggest that schizophrenics suffer from an impairment in the interhemispheric transfer (IHT) of information, methodological weaknesses in these studies preclude clear interpretation of their results. This study addresses these criticisms in order to provide a clearer test of the IHT theory. Schizophrenics, depressives, normal controls, and normals with schizoid tendencies were assessed on five measures of IHT (verbal and nonverbal dichotic listening, intermanual transfer, bimanual block design, finger sequence repetition) and two measures of unilateral hemispheric processing (lateral eye movements, auditory thresholds). Results consistently failed to support an IHT deficit interpretation of schizophrenia. Schizoid normals had a significantly greater right-ear advantage on verbal dichotic listening than both psychiatric groups, a result suggesting enhanced left-hemisphere activation in schizoid normals. It is concluded that the IHT theory requires stronger empirical substantiation than has been obtained to date to warrant further consideration as a central theory of schizophrenia.

Adult↗

Stapes surgery in relation to age.

This prospective study aims to evaluate the efficacy of stapedotomy in relation to age. Eighty-four ears of 82 consecutive patients who underwent stapedotomy were studied. Patients were divided into five groups according to their age. In each patient, we evaluated the pre- and postoperative auditory thresholds, according to the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology - Head and Neck Surgery guidelines. Statistically significant (P < 0.05) differences between the pre- and postoperative air conduction thresholds were observed in all groups. Statistically significant reductions of air-bone gap were observed at lower-medium frequencies (250, 500 and 1000 Hz) in the elderly as well as in the younger patients. We did not find a higher susceptibility of the inner ear to surgical trauma in the elderly in comparison to the younger patients. Our data show that stapedotomy results in older adults are comparable to those obtained in the younger, without an increased incidence of complications.

Adult↗